The proposed research investigates the potential genetic moderators of psychological and physical adjustment to the common life stressor of divorce. Although most people are resilient in the face of divorce, a subset of adults becomes stuck on pathways toward maladaptive outcomes, making the association between divorce, mood disturbances, and physical health a significant public health concern. The primary goal of this project is to collect deoxyribonucleic acid (DNA) from 190 adults (156 of Caucasian/European American descent) who have experienced a recent marital separation in order to (1) investigate candidate polymorphisms in four serotonin genes that may interact with the psychosocial context of marital separation to moderate changes in mood symptoms over a 9-month period and (2) investigate the role of genes within the inflammation system that may moderate changes in blood pressure (BP) reactivity to a divorce-specific laboratory challenge paradigm. By studying the potential genetic moderators of divorce adjustment, this work can provide new insights into who fares well or poorly following the end of marriage. There is consensus in the fields of genetic epidemiology and molecular psychiatry that the study of genotypic effects on psychological and biological end- points of interest can be greatly enhanced through improved measurement of the psychosocial environment. Thus, by carefully measuring adults'psychological responses to their separation and degree of reported stress, this work has the potential to enhance what is known about the effects of gene-environment (G X E) interactions on psychological and health-related phenotypes of interest. The proposed research is one the first prospective investigations of how G X E interactions may limit or promote emotional and biological recovery over time. Using a planned missingness design (intended to decrease participant attrition), adults will be studied at four occasions over a 9-month period. Simulation studies of this sampling approach reveal that the proposed study will be adequately powered to detect small G X E interaction effects on changes in mood symptoms and BP reactivity. In combination, the study of genes in both the serotonin and inflammation systems, the detailed assessment of the psychosocial context of divorce, and the prospective sampling and data analyses will make the proposed study unique to the existing literature and one with potential for high scientific yield in an understudied area of public health significance. This research will contribute to the growing effort to identify the precise effect size estimates in G X E studies of mood disturbances, as well as newly emerging research in psychosomatic medicine that combines genes, psychological variables, and biological response patterns of interest. There are many reasons to believe that genes in the emotion and inflammation systems interact to produce both increased depression and heightened BP responses, and the proposed investigation has promise to make timely and important contributions to this growing area of research. PUBLIC HEALTH RELEVANCE: Divorce is among the most stressful life events a person can experience, and a significant proportion of adults develop diagnosable mental and physical health problems following the end of marriage. By collecting deoxyribonucleic acid (DNA) from 190 recently separated adults, this project seeks to determine if some people are at unique risk for poor outcomes in the wake of this stressful experience. A better understanding of the associations between the psychological stress of divorce, genetic risk, and health is critical for developing improved prevention and treatment programs.